Abstract |
In this study, we investigated whether an orally active chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl] acetamide ( NK3201), prevents intimal hyperplasia in carotid arteries injured by a balloon catheter in dog. Each dog was administered NK3201 (1 mg/kg per day, p.o.) or placebo beginning 5 days before balloon injury and continuing through the experiments. Four weeks after balloon injury, NK3201 did not affect the plasma renin and angiotensin-converting enzyme activities. The chymase activity was significantly increased in the injured arteries, whereas the angiotensin-converting enzyme activity was not. NK3201 significantly reduced the chymase activity in the injured arteries. The intimal area in the placebo- and NK3201-treated group and was 0.46 +/- 0.06 and 0.24 +/- 0.04 mm2, respectively, and this difference was significant. In this study, we demonstrated for the first time that a chymase inhibitor prevented the development of intimal hyperplasia in the balloon-injured arteries.
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Authors | Shinji Takai, Hiroshi Sakonjo, Kohzo Fukuda, Denan Jin, Masato Sakaguchi, Keiichi Kamoshita, Koichi Ishida, Yoshikazu Sukenaga, Mizuo Miyazaki |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 304
Issue 2
Pg. 841-4
(Feb 2003)
ISSN: 0022-3565 [Print] United States |
PMID | 12538841
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetamides
- NK3201
- Pyrimidines
- Serine Proteinase Inhibitors
- Serine Endopeptidases
- Chymases
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Topics |
- Acetamides
(pharmacology, therapeutic use)
- Animals
- Carotid Artery, Common
(drug effects, enzymology, pathology)
- Catheterization
(adverse effects)
- Chymases
- Dogs
- Hyperplasia
- Pyrimidines
(pharmacology, therapeutic use)
- Serine Endopeptidases
(metabolism)
- Serine Proteinase Inhibitors
(pharmacology, therapeutic use)
- Tunica Intima
(drug effects, enzymology, injuries, pathology)
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